A clinical need exists for the development of accurate and efficient dose calculation methods for clinical treatment planning in external beam radiotherapy. Due to recent advances in image guided localization techniques and the development of more precise beam delivery methods such as Intensity Modulated Radiation Therapy (IMRT), the potential exists to substantially reduce margins and improve dose conformity. However, most dose calculation methods in clinical use today employ approximations that limit their accuracy and scope of use, especially with narrow beams in the presence of heterogeneities. As a result, industry is moving rapidly towards the clinical adoption of Monte Carlo. However, Monte Carlo calculations are time consuming, limiting their effectiveness for clinical treatment planning. In the Phase I research, a novel deterministic dose calculation method, which solves the differential form of the governing transport equations for neutral and charged particles, was validated against Monte Carlo for patient specific prostate and head- and-neck cases. The results indicated that the proposed approach is as accurate as Monte Carlo, and can provide higher spatial precision. Similarly, the proposed approach was shown to be much faster than Monte Carlo, which can translate to improved accuracy in a clinical setting. In Phase II, a commercially viable dose calculation system will be developed which can be integrated into clinical treatment planning systems, with multi-fold performance gains over the Phase I prototype. Validation cases will be performed by M.D. Anderson Cancer Center, using both experimental data and retrospective patient plans. By providing a combination of speed and accuracy superior to existing clinical dose calculation methods, the Phase II product has the potential to improve quality of care for the approximately 650,000 patients receiving photon beam radiotherapy each year in the U.S., and for many more worldwide. In addition, since the Phase II product is based on first principles numerical methods, it can ultimately be adapted to other radiotherapy modalities. By providing physicians with more accurate dose assessments, the Phase II research has the potential to improve the quality of care for the 650,000 people receiving external beam radiotherapy in the United States each year. Through generally applicable algorithms, the resulting product can ultimately be migrated towards clinical treatment planning for other radiotherapy modalities. [unreadable] [unreadable] [unreadable]